Neuroscience Research 152 (2020) 1–2

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Neuroscience Research
journal homepage: www.elsevier.com/locate/neures

Editorial

Technologies advancing neuroscience

“Progress in science depends on new techniques, new discover- Optogenetics has been one of the most impactful techniques in
ies and new ideas, probably in that order.” –Sydney Brenner modern systems neuroscience. Nakajima and Schmitt (2020) dis-
cuss how combining this approach to activate or inhibit specific
When Sydney Brenner first uttered his famous quote 40 years
types of neurons with high-density physiology and well-designed
ago he was reflecting on a decade of rapid progress, primarily
behavioral tasks can lend novel insights into cognition. Chen et al.
driven by tools based on a deepening understanding of molec-
(2020) describe approaches to take optogenetics one step further.
ular biology. The first twenty years of this century have seen
They review recent work based on chemically-synthesized upcon-
advances in molecular biology, chemistry, optics and computa-
version nanoparticles which allow the use of tissue-penetrating
tional approaches converge to drive rapid progress in neuroscience;
near-infrared light to control neuronal activity in the absence of
making experiments that seemed impossible at the turn of the cen-
invasive optical fibers. Yamada et al. (2020) describe a different
tury now seem routine. The importance of these advances is further
application of light in the brain; the control of gene expression.
reflected in the initiatives across the globe which aim to acceler-
These authors highlight how genetically-defined photoactivatable
ate our ability to image, manipulate and ultimately treat the brain
actuator molecules can be employed for the exquisite temporal and
through novel approaches that are more precise and less invasive.
spatial control of genetic programs.
To review this progress, we have asked experts in tool development
The theme of targeting manipulations in space and time is
and application to contribute to this issue and update our readers on
reflected in the final two contributions. Blankvoort et al. (2020)
the current state and future goals of these domains. The review arti-
review how the specificity of transgene expression, key to precise
cles we have collected here touch on three major themes: advances
experimental manipulations, can be improved through the use of
in our abilities to image activity in the brain, advances in the use
enhancer elements from the genome. One huge advantage of this
of light to control the brain, and finally, improvements in targeting
Enhancer-Driven Gene Expression approach is the small size of
manipulations both in space and time.
the enhancer elements which allows specific targeting with viral
First, Shen, Campbell and colleagues (Shen et al., 2020) review
vectors. Finally, Takeuchi and Berényi (2020) tackle a more trans-
new additions to the toolkit of fluorescent indicators for the imag-
lational problem; commenting on how the growing understanding
ing of neural activity. Coming from the tool developer’s side, the
of the links between neurological disorders and pathological oscil-
authors beautifully describe approaches that experimentalists can
lations in the brain create new therapeutic opportunities. They
embrace to generate new discoveries. Roome and Kuhn (2020)
review how advances in brain stimulation technologies enable
focus their review more specifically on voltage imaging, highlight-
temporally and spatially specific interventions which may combat
ing advances in the synthetic pure electrochromic voltage-sensitive
these pathologies and offer novel treatments for disease.
ANNINE dyes. The benefits of these dyes in terms of high voltage
We hope this collection of reviews will serve as a useful ref-
sensitivity and low phototoxicity is discussed, as well as their ability
erence of the current state of the art approaches, as well as an
to be used in combination with green indicators, such as GCaMP6.
inspiration for the discoveries and ideas that these tools will bring
They offer some examples of this exquisite combination, simulta-
us in the coming years.
neously imaging dendritic calcium and somatic electrical activity
in single Purkinje cells.
Activity in neurons reflects synaptic input and Choi et al. References
(2020) bridge this gap by highlighting recently developed methods
to visualize and manipulate active neurons and synapses. These Blankvoort, S., Descamps, L.A.L., Kentros, C., 2020. Enhancer-Driven Gene Expression
approaches allow neuroscientists to visualize activity at levels of (EDGE) enables the generation of cell type specific tools for the analysis of neural
circuits. Neurosci. Res. 152, 78–86.
specificity that until recently seemed impossible. Neurons and Chen, S., Jiang Wu, J., Cai, A., Kim, H.J., 2020. Towards minimally invasive deep brain
synapses respond to the transmitters released at their membranes. stimulation and imaging: a near-infrared upconversion approach. Neurosci. Res.
Wu and Li (2020) discuss recent progress in the development and 152, 59–65.
Choi, J.-E., Kim, J., Kim, J., 2020. Capturing activated neurons and synapses. Neurosci.
application of new methods for detecting purinergic transmitters,
Res. 152, 25–34.
focusing on the new types of genetically encoded optical tools. Nakajima, M., Schmitt, L.I., 2020. Understanding the circuit basis of cognitive func-
These genetically encoded sensors once again increase the reso- tions using mouse models. Neurosci. Res. 152, 44–58.
Roome, C.J., Kuhn, B., 2020. Voltage imaging with ANNINE dyes and two-photon
lution of these experiments in both space and time.
microscopy of Purkinje dendrites in awake mice. Neurosci. Res. 152, 15–24.

https://doi.org/10.1016/j.neures.2020.02.006
0168-0102/© 2020 Published by Elsevier B.V.
2 Editorial / Neuroscience Research 152 (2020) 1–2

Shen, Y., Nasu, Y., Shkolnikov, I., Kim, A., Campbell, R.E., 2020. Engineering geneti- Kazumasa Z. Tanaka ∗
cally encoded fluorescent indicators for imaging of neural activity: progress and Okinawa Institute of Science and Technology
prospects. Neurosci. Res. 152, 3–14.
Takeuchi, Y., Berényi, A., 2020. Oscillotherapeutics – time-targeted interventions in Graduate University,
epilepsy and beyond. Neurosci. Res. 152, 87–107. 1919-1 Tancha, Onna-son, Kunigami-gun,
Wu, Z., Li, Y., 2020. New frontiers in probing the dynamics of purinergic transmitters Okinawa, 904-0495, Japan
in vivo. Neurosci. Res. 152, 35–43.
Yamada, M., Nagasaki, S.C., Ozawa, T., Imayoshi, I., 2020. Light-mediated control of
∗ Correspondingauthors.
gene expression in mammalian cells. Neurosci. Res. 152, 66–77.
E-mail addresses:
Thomas J. McHugh ∗ thomas.mchugh@riken.jp (T.J. McHugh),
RIKEN Center for Brain Science, kazumasa.tanaka@oist.jp (K.Z. Tanaka).
Wako, Saitama, 351-0198, Japan